Proliferative skin diseases, such as psoriasis, eczema, mycosis fungoides, actinic keratosis, and lichen planus, are known to effect one to two percent of the U.S. population, with as many as 150,000-260,000 new cases occurring annually ("Research Needs in 11 Major Areas in Dermatology" I. Psoriasis. J. Invest. Dermatol. 73:402-13, 1979). One method used to treat the rapid proliferation of skin cells is phototherapy, which utilizes optical absorption of ultraviolet (UV) radiation by the skin to kill rapidly growing cells and arrest proliferation. At present, both UVA and UVB therapy, which expose the skin to UV radiation between 320-400 nm (UVA radiation) or 290-320 nm (UVB radiation), are effective and widely used. PUVA therapy, a form of photochemotherapy which involves repeated topical application of psoralen or a psoralen-based compound to an affected region of skin, followed by exposure of that region to UVA radiation, is also widely used. Another method used to treat proliferative skin diseases, particularly psoriasis and mycosis fungoides, is photodynamic therapy (PDT). In this method, a photosensitizing agent, which is a drug selectively retained in carcinoma cells, is administered to a patient. Following absorption of light (typically between 320-700 nm, depending on the drug) the photosensitizing agent undergoes a photochemical reaction, resulting in the production of cytotoxic singlet oxygen which eventually leads to tumor vessel destruction in the skin (Anderson, et al., Arch. Dermatol. 128:1631-1636, 1992).
Prolonged treatment for proliferative skin diseases using these types of therapies can, however, result in significant acute and chronic adverse effects including erythema, pruritus, skin cancer, and chronic light-induced damage of the skin (Stern et al., N.E. J. Med. 300:809-812, 1979).
It is therefore desirable to reduce the number of times the skin is exposed to radiation during phototherapy. PUVA therapy (Wolff, Pharmacol. Ther. 12:381, 1981), and frequent alternation of PUVA therapy with other treatments (Parris et al., The Science of Photomedicine, Regan et al., eds., 1982, p. 615) have been suggested as methods to reduce the cumulative number of iterations (typically around 25) required for successful treatment. Another method used to decrease the number of phototherapy treatments involves increasing the optical fluence during therapy (Honigsmann et al., Dermatology in General Medicines, 3rd ed, T. B. Fitzpatrick et al., eds., 1533-1558, 1987; Ryatt, et al., J. Am. Acad. Dermatol. 9:558-562, 1983). Up to a threefold reduction in the time required for the affected region to clear is possible when isolated plaques are exposed to radiation levels between two and three times the minimal erythema dose (MED), defined as the level of optical fluence resulting in the onset of erythema (Parrish et al., J. Invest. Dermatol. 76:359-362, 1981).
Because both UVA and UVB radiation are harmful to normal skin, the tolerable limit of treatment aggressiveness is ultimately limited by adverse effects resulting from the cumulative exposure of the skin to UV radiation. Presently, the level of UV radiation is kept as high as possible during phototherapeutic treatments, just less than the level causing painful sunburn.
In order to reduce the effects of increased exposure to UV radiation during phototherapy, it is possible, but impractical, to apply sunscreens to all the non-affected skin areas which surround sites of affected skin; most proliferative skin diseases involve tens or hundreds of affected regions which are randomly located over the body. In addition, during PDT there is often appreciable uptake of the photosensitizing agent in the non-affected regions of skin, making it desirable to protect these regions from drug-activating radiation.